Saccharide foamable compositions

ABSTRACT

A foamable composition, containing a saccharide for use in the treatment of various disorders including: water, a saccharide, about 0.2% to about 5% by weight of a surface-active agent, about 0.01% to about 5% by weight of at least one polymeric agent selected from a bio-adhesive agent, a gelling agent, a film forming agent and a phase change agent, and a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the total composition.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.11/430,437 filed May 9, 2006, which claims the benefit of U.S.Provisional Patent Application No. 60/679,020 filed May 9, 2005, and thebenefit of U.S. Provisional Patent Application No. 60/784,793, filed onMar. 21, 2006, entitled Polyol Foamable Vehicle and PharmaceuticalCompositions Thereof, which are incorporated herein by reference.

BACKGROUND OF THE INVENTION

This invention relates to foamable pharmaceutical and cosmeticcompositions.

External topical administration is an important route for theadministration of drugs in disease treatment. Many groups of drugs,including, for example, antibiotic, anti-fungal, anti-inflammatory,anesthetic, analgesic, anti-allergic, corticosteroid, retinoid andanti-proliferative medications are generally administered in semisolidpreparations. While semi-solid compositions, such as cream and ointmentare commonly used by consumers, new forms are desirable in order toachieve better control of the application, while maintaining orbestowing the skin beneficial properties of such products.

There remains an unmet need for improved, easy to use, stable andnon-irritating foam formulations, intended for treatment of dermal andmucosal tissues, with unique therapeutic properties.

SUMMARY OF THE INVENTION

The present invention is geared towards providing an improved externaltopical administration tool.

According to the present invention there is provided a foamablesaccharide composition including: (i) water, (ii) a saccharide, (iii)about 0.2% to about 5% by weight of a surface-active agent, (iv) about0.01% to about 5% by weight of at least one polymeric agent selectedfrom a bio-adhesive agent, a gelling agent, a film forming agent and aphase change agent, and (v) a liquefied or compressed gas propellant ata concentration of about 3% to about 25% by weight of the totalcomposition.

According to further embodiments of the present invention, thesaccharide is selected from the group consisting of a saccharide, amonosaccharide, a disaccharide, an oligosaccharide and a sugar alcohol;and naturally occurring saccharide mixtures, such as honey.

According to still further embodiments of the present invention, thesaccharide composition further including a foam adjuvant, selected fromthe group of a long chain fatty alcohol and a long chain fatty acid.

According to yet further embodiments of the present invention, thesaccharide composition further includes a hydrophobic solvent.

According to still further embodiments of the present invention, thecomposition is in the form of an oil in water emulsion; and wherein theHLB of surface-active agent is between about 9 and about 14.

According to further embodiments of the present invention, thesaccharide composition further including at least one component,selected from the group consisting of a keratolytic agent, and a polarsolvent.

According to still further embodiments of the present invention, thesaccharide composition further containing at least one active agent,selected from the group of: an active herbal extract, an acaricide, anage spot and keratose removing agent, an allergen, an analgesic agent, alocal anesthetic, an antiacne agent, an antiallergic agent, an antiagingagent, an antibacterial agent, an antibiotic agent, an antiburn agent,an anticancer agent, an antidandruff agent, an antidepressant, anantidermatitis agent, an antiedemic agent, an antihistamine, anantihyperkeratolyte agent, an antiinflammatory agent, an antiirritant,an antilipemic agent, an antimicrobial agent, an antimycotic agent, anantiproliferative agent, an antioxidant, an anti-wrinkle agent, anantipruritic agent, an antipsoriatic agent, an antirosacea agent, anantiseborrheic agent, an antiseptic agent, an antiswelling agent, anantiviral agent, an antiyeast agent, an astringent, a topicalcardiovascular agent, a chemotherapeutic agent, a corticosteroid, adicarboxylic acid, a disinfectant, a fungicide, a hair growth regulator,a hormone, a hydroxy acid, an immunosuppressant, an immunoregulatingagent, an insecticide, an insect repellent, a keratolytic agent, alactam, a metal, a metal oxide, a mitocide, a neuropeptide, anon-steroidal anti-inflammatory agent, an oxidizing agent, apediculicide, a photodynamic therapy agent, a retinoid, a scabicide, aself tanning agent, a skin whitening agent, a vasoconstrictor, avasodilator, a vitamin, a vitamin D derivative, a wound healing agentand a wart remover.

According to yet further embodiments of the present invention, thesaccharide composition is hygroscopic.

According to still further embodiments of the present invention, theconcentration of the saccharide is adjusted to provide a Aw value of thefoamable composition selected from the ranges of (1) about 0.8 and about0.9; (2) about 0.7 and about 0.8; and (3) less than about 0.7.

According to further embodiments of the present invention, thehygroscopic pharmaceutical composition further includes atherapeutically effective concentration of an anti-infective agent

According to still further embodiments of the present invention, theanti-infective agent, selected from the group of an antibiotic agent, anantibacterial agent, an antifungal agent, an agent that controls yeast,an antiviral agent and an antiparasitic agent.

According to yet further embodiments of the present invention, theantibiotic agent is selected from the group consisting of a beta-lactamantibiotic, an aminoglycoside, an ansa-type antibiotic, ananthraquinone, an azole, metronidazole, an antibiotic glycopeptide, amacrolide, erythromycin, clindamycin, an antibiotic nucleoside, anantibiotic peptide, polymyxin B, an antibiotic polyene, an antibioticpolyether, an antibiotic quinolone, an antibiotic steroid, fucidic acid,mupirocin, chloramphenicol, a sulfonamide, tetracycline, an antibioticmetal, silver, copper, zinc, mercury, tin, lead, bismuth, cadmium,chromium, an oxidizing agent, iodine, iodate, a periodate, ahypochlorite, a permanganate, a substance that release free radicalsand/or active oxygen, a cationic antimicrobial agent, a quaternaryammonium compound, a biguanide, chlorohexidine, a triguanide, abisbiguanide, a polymeric biguanide, a naturally occurring antibioticcompound and analogs, derivatives, salts, ions and complexes thereof.

According to still further embodiments of the present invention, theantifungal agent is useful in the treatment of an infection ofdermatophytosis, microsporum, trichophyton and epidermophytoninfections, candidiasis, oral candidiasis (thrush), yeast and candida.

According to still further embodiments of the present invention, theantifungal agent is selected from the group consisting of a polyene,natamycin, nystatin; an allylamine, naftifine, terbinafine; animidazole, bifonazole, clotrimazole, econazole, fenticonazole,ketocanazole, miconazole, oxiconazole; a diazole, a triazoles,fluconazole, itraconazole, terconazole, tolnaftate, ciclopirox,undecylenic acid, sulbentine, griseofulvin, Amphotericin B, flucytosine(5FC), a morpholine compound, amorolfine, and the related morpholinesand analogs, derivatives and salts thereof, and any combination thereofat a therapeutically effective concentration.

According to a second embodiment of the present invention, there isprovided a method of treatment of a disorder of the skin, a bodysurface, a body cavity or mucosal surface, the nasal cavity, the mouth,the eye, the ear canal, the vagina and the rectum, consisting ofadministering the saccharide compositions to a target site of treatment.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a foamable composition, containing asaccharide for use in the treatment of various disorders. According toone or more embodiments of the present invention, the foamablesaccharide composition includes:

a. a saccharide aqueous solution;

b. about 0.2% to about 5% by weight of a surface-active agent;

c. about 0.01% to about 5% by weight of at least one polymeric agent;and

d. a liquefied or compressed gas propellant at a concentration of about3% to about 25% by weight of the total composition.

All % values are provided on a weight (w/w) basis.

Water and optional ingredients are added to complete the total mass to100%.

Upon release from an aerosol container, the foamable composition formsan expanded foam suitable for the treatment of an infected surface andfor topical administration to the skin, a body surface, a body cavity ora mucosal surface.

Saccharide

Saccharides vary from simple sugars containing from three to sevencarbon atoms to very complex polymers.

Exemplary saccharides include, but are not limited to monosaccharide,disaccharides, oligosaccharides and sugar alcohols, which possesshygroscopic properties.

A monosaccharide is a simple sugar that cannot be hydrolysed to smallerunits. Empirical formula is (CH₂O)_(n) and range in size from trioses(n=3) to heptoses (n=7). Exemplary monosaccharide compounds are ribose,glucose, fructose and galactose.

Disaccharides are made up of two monosaccharides joined together, suchas sucrose, maltose and lactose.

A sugar alcohol (also known as a polyol, polyhydric alcohol, orpolyalcohol) is a hydrogenated form of saccharide, whose carbonyl group(aldehyde or ketone, reducing sugar) has been reduced to a primary orsecondary hydroxyl group. They are commonly used for replacing sucrosein foodstuffs, often in combination with high intensity artificialsweeteners to counter the low sweetness. Some exemplary sugar alcohols,which are suitable for use according to the present invention aremannitol, sorbitol, xylitol, maltitol, lactitol. (Maltitol and lactitolare not completely hydrogenated compounds—they are a monosaccharidecombined with a polyhydric alcohol).

In an embodiment of the present invention, the concentration of thesaccharide in the foamable composition of the present invention isbetween about 20% and about 80%. In certain embodiments, theconcentration of the saccharide is between about 50% and about 80%. Anexemplary saccharide solution, suitable according to the presentinvention contains 70% sorbitol in water. Another example is honey,which is composed primarily of sugars and water. The average honeycontains about 80% saccharides and about 17% water, and the primarysaccharides are fructose and glucose.

Polymeric Agent

The composition of the present invention contains a polymeric agent. Ithas been documented that the presence of a polymeric agent is desirablefor the creation of foam, having fine bubble structure, which does notreadily collapse upon release from the pressurized aerosol can. Thepolymeric agent serves to stabilize the foam composition and to controldrug residence in the target organ. Preferably, the polymeric agent isselected from the group consisting of a bioadhesive agent, a gellingagent, a film forming agent and a phase change agent.

Exemplary polymeric agents include, in a non-limiting manner,naturally-occurring polymeric materials, such as locust bean gum, sodiumalginate, sodium caseinate, egg albumin, gelatin agar, carrageenin gum,sodium alginate, xanthan gum, quince seed extract, tragacanth gum, guargum, cationic guars, hydroxypropyl guar gum, starch, amine-bearingpolymers such as chitosan; acidic polymers obtainable from naturalsources, such as alginic acid and hyaluronic acid; chemically modifiedstarches and the like, carboxyvinyl polymers, polyvinylpyrrolidone,polyvinyl alcohol, polyacrylic acid polymers, polymethacrylic acidpolymers, polyvinyl acetate polymers, polyvinyl chloride polymers,polyvinylidene chloride polymers and the like.

Further exemplary gelling agents include the acrylic acid/ethyl acrylatecopolymers and the carboxyvinyl polymers. These resins consistessentially of a colloidal water-soluble polyalkenyl polyethercrosslinked polymer of acrylic acid crosslinked with a crosslinkingagent such as polyallyl sucrose or polyallyl pentaerythritol. Examplesinclude Carbopol® 934, Carbopol® 940, Carbopol® 950, Carbopol® 980,Carbopol® 951 and Carbopol® 981. Carbopol® 934 is a water-solublepolymer of acrylic acid crosslinked with a polyallyl ether of sucrose.

Additional exemplary polymeric agents include semi-synthetic polymericmaterials such as cellulose ethers, such as methylcellulose,hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethylcellulose, hydroxy propylmethyl cellulose, methylhydroxyethylcellulose,methylhydroxypropylcellulose, hydroxyethylcarboxymethylcellulose,carboxymethyl cellulose, carboxymethylcellulosecarboxymethylhydroxyethylcellulose, and cationic celluloses.Polyethylene glycol, having molecular weight of 1000 or more (e.g., PEG1,000, PEG 4,000, PEG 6,000 and PEG 10,000) also have gelling capacityand while they are considered as “additional polar solvents”, asdetailed herein, they are also considered polymeric agents.

Mixtures of the above polymeric agents are contemplated.

The concentration of the polymeric agent should be selected so that thecomposition, after filling into aerosol canisters, is flowable, and canbe shaken in the canister. In one or more embodiments, the concentrationof the polymeric agent is selected such that the viscosity of thecomposition, prior to filling of the composition into aerosol canisters,is less than 12,000 CPs, and more preferably, less than 10,000 CPs.

Surface-active Agent

The composition of the present invention further contains asurface-active agent. Surface-active agents (also termed “surfactants”)include any agent linking oil and water in the composition, in the formof emulsion. A surfactant's hydrophilic/lipophilic balance (HLB)describes the emulsifier's affinity toward water or oil. HLB is definedfor non-ionic surfactants. The HLB scale ranges from 1 (totallylipophilic) to 20 (totally hydrophilic), with 10 representing an equalbalance of both characteristics. Lipophilic emulsifiers formwater-in-oil (w/o) emulsions; hydrophilic surfactants form oil-in-water(o/w) emulsions. The HLB of a blend of two emulsifiers equals the weightfraction of emulsifier A times its HLB value plus the weight fraction ofemulsifier B times its HLB value (weighted average).

According to one or more embodiments of the present invention, thesurface-active agent has a hydrophilic lipophilic balance (HLB) betweenabout 9 and about 14, which is the required HLB (the HLB required tostabilize an O/W emulsion of a given oil) of most oils and hydrophobicsolvents. Thus, in one or more embodiments, the composition contains asingle surface active agent having an HLB value between about 9 and 14,and in one or more embodiments, the composition contains more than onesurface active agent and the weighted average of their HLB values isbetween about 9 and about 14. Yet, in other embodiments, when a water inoil emulsion is desirable, the composition contains one or more surfaceactive agents, having an HLB value between about 2 and about 9.

Preferably, the composition of the present invention contains anon-ionic surfactant. Nonlimiting examples of possible non-ionicsurfactants include polysorbates, such as polyoxyethylene (20) sorbitanmonostearate (Tween 60) and poly(oxyethylene) (20) sorbitan monooleate(Tween 80); poly(oxyethylene) (POE) fatty acid esters, such as Myrj 45,Myrj 49, Myrj 52 and Myrj 59; poly(oxyethylene) alkylyl ethers, such aspoly(oxyethylene) cetyl ether, poly(oxyethylene) palmityl ether,polyethylene oxide hexadecyl ether, polyethylene glycol cetyl ether,brij 38, brij 52, brij 56 and brij W1; sucrose esters, partial esters ofsorbitol and its anhydrides, such as sorbitan monolaurate and sorbitanmonolaurate; mono or diglycerides, isoceteth-20, and mono-, di- andtri-esters of sucrose with fatty acids (sucrose esters).

In certain case, the surface active agent is selected from the group ofcationic, zwitterionic, amphoteric and ampholytic surfactants, such assodium methyl cocoyl taurate, sodium methyl oleoyl taurate, sodiumlauryl sulfate, triethanolamine lauryl sulfate and betaines.

In one or more embodiments of the present invention, the surface-activeagent includes at least one non-ionic surfactant. Ionic surfactants areknown to be irritants. Therefore, non-ionic surfactants are preferred inapplications including sensitive tissue such as found in most mucosaltissues, especially when they are infected or inflamed. We havesurprisingly found that non-ionic surfactants alone provide foams ofexcellent quality, i.e. a score of “E” according to the grading scalediscussed herein below.

Thus, in a preferred embodiment, the surface active agent, thecomposition contains a non-ionic surfactant, or a mixture of non-ionicsurfactants as the sole surface active agent. Yet, in additionalembodiments, the foamable composition includes a mixture of at least onenon-ionic surfactant and at least one ionic surfactant in a ratio in therange of about 100:1 to 6:1. In further embodiments, surface activeagent comprises a combination of a non-ionic surfactant and an ionicsurfactant, at a ratio of between 1:1 and 20:1.

The concentration of the surface active agent is between about 0.1% andabout 5%.

Hydrophobic Solvent

Optionally, the foamable carrier further contains at least onehydrophobic solvent. The identification of a “hydrophobic solvent”, asused herein, is not intended to characterize the solubilizationcapabilities of the solvent for any specific active agent or any othercomponent of the foamable composition. Rather, such information isprovided to aid in the identification of materials suitable for use as apart in the foamable compositions described herein.

A “hydrophobic solvent” as used herein refers to a material havingsolubility in distilled water at ambient temperature of less than about1 gm per 100 mL, more preferable less than about 0.5 gm per 100 mL, andmost preferably less than about 0.1 gm per 100 mL.

In one or more embodiments, the hydrophobic organic carrier is an oil,such as mineral oil, isopropyl palmitate, isopropyl isostearate,diisopropyl adipate, diisopropyl dimerate, maleated soybean oil, octylpalmitate, cetyl lactate, cetyl ricinoleate, tocopheryl acetate,acetylated lanolin alcohol, cetyl acetate, phenyl trimethicone, glyceryloleate, tocopheryl linoleate, wheat germ glycerides, arachidylpropionate, myristyl lactate, decyl oleate, propylene glycolricinoleate, isopropyl lanolate, pentaerythrityl tetrastearate,neopentylglycol dicaprylate/dicaprate, isononyl isononanoate,isotridecyl isononanoate, myristyl myristate, triisocetyl citrate, octyldodecanol, unsaturated or polyunsaturated oils, such as olive oil, cornoil, soybean oil, canola oil, cottonseed oil, coconut oil, sesame oil,sunflower oil, borage seed oil, syzigium aromaticum oil, hempseed oil,herring oil, cod-liver oil, salmon oil, flaxseed oil, wheat germ oil,evening primrose oils; essential oils; and silicone oils, such asdimethicone, cyclomethicone, polyalkyl siloxanes, polyaryl siloxanes,polyalkylaryl siloxanes and polyether siloxane copolymers,polydimethylsiloxanes (dimethicones) andpoly(dimethylsiloxane)-(diphenyl-siloxane) copolymers.

Foam Adjuvant

Optionally, a foam adjuvant is included in the foamable carriers of thepresent invention to increase the foaming capacity of surfactants and/orto stabilize the foam. In one or more embodiments of the presentinvention, the foam adjuvant agent includes fatty alcohols having 15 ormore carbons in their carbon chain, such as cetyl alcohol and stearylalcohol (or mixtures thereof). Other examples of fatty alcohols arearachidyl alcohol (C20), behenyl alcohol (C22), 1-triacontanol (C30), aswell as alcohols with longer carbon chains (up to C50). Fatty alcohols,derived from beeswax and including a mixture of alcohols, a majority ofwhich has at least 20 carbon atoms in their carbon chain, are especiallywell suited as foam adjuvant agents. The amount of the fatty alcoholrequired to support the foam system is inversely related to the lengthof its carbon chains. Foam adjuvants, as defined herein are also usefulin facilitating improved spreadability and absorption of thecomposition.

In one or more embodiments of the present invention, the foam adjuvantagent includes fatty acids having 16 or more carbons in their carbonchain, such as hexadecanoic acid (C16) stearic acid (C18), arachidicacid (C20), behenic acid (C22), octacosanoic acid (C28), as well asfatty acids with longer carbon chains (up to C50), or mixtures thereof.As for fatty alcohols, the amount of fatty acids required to support thefoam system is inversely related to the length of its carbon chain.

Optionally, the carbon atom chain of the fatty alcohol or the fatty acidmay have at least one double bond. A further class of foam adjuvantagent includes a branched fatty alcohol or fatty acid. The carbon chainof the fatty acid or fatty alcohol also can be substituted with ahydroxyl group, such as 12-hydroxy stearic acid.

Keratolytic Agent

In an embodiment of the present invention, the saccharide compositioncontains a keratolytic agent. The term “keratolytic agent” is usedherein to mean a compound which loosens and removes the stratum corneumof the skin, or alters the structure of the keratin layers of skin.Keratolytic agents are used in the treatment of many dermatologicaldisorders, which involve dry skin, hyperkeratiinization (such aspsoriasis), skin itching (such as xerosis), acne and rosacea. Suitablekeratolytic agents include but are not limited to N-acetylcysteine,azelaic acid, cresols, dihydroxy benzene compounds, such as resorcinoland hydroquinone, alpha-hydroxy acids, such as lactic acid and glycolicacid, phenol, pyruvic acid, resorcinol, sulfur, salicylic acid, retinoicacid, isoretinoic acid, retinol, retinal, urea and derivatives, esters,salts and mixtures thereof.

Polar Solvent/Penetration Enhancer

In an embodiment of the present invention, the saccharide compositioncontains a polar solvent. In one or more embodiments, the polar solventis a polyol, i.e., an organic substance that contains at least twohydroxy groups in its molecular structure. Examples of polyols includepropylene glycol (e.g., 1,2-propylene glycol and 1,3-propylene glycol),butanediol (e.g., 1,2-butanediol, 1,3-butanediol, 2,3-butanediol and1,4-butanediol), butanediol (e.g., 1,3-butanediol and 1,4-butenediol),butynediol, pentanediol (e.g., pentane-1,2-diol, pentane-1,3-diol,pentane-1,4-diol, pentane-1,5-diol, pentane-2,3-diol andpentane-2,4-diol), hexanediol (e.g., hexane-1,6-diol hexane-2,3-diol andhexane-2,56-diol), octanediol (e.g., 1,8-octanediol), neopentyl glycol,2-methyl-1,3-propanediol, diethylene glycol, triethylene glycol,tetraethylene glycol, dipropylene glycol, dibutylene glycol, glycerin,butane-1,2,3-triol, butane-1,2,4-triol and hexane-1,2,6-triol.

Additional polar solvents that can be contained in the composition ofthe present invention include dimethyl isosorbide, tetrahydrofurfurylalcohol polyethyleneglycol ether (glycofurol), DMSO, pyrrolidones, (suchas N-Methyl-2-pyrrolidone and 1-Methyl-2-pyrrolidinone), ethyl proxitol,dimethylacetamide (DMAc) and alpha hydroxy acids, such as lactic acid,glycolic acid and polyethylene glycol. Notably, polar solvents, asexemplified above generally possess skin penetration enhancingproperties.

Additional Components

In an embodiment of the present invention, a composition of the presentinvention includes one or more additional components. Such additionalcomponents include but are not limited to anti perspirants, anti-staticagents, buffering agents, bulking agents, chelating agents, cleansers,colorants, conditioners, deodorants, diluents, dyes, emollients,fragrances, hair conditioners, humectants, occlusive agents, oils,penetration enhancers, pearlescent aids, perfuming agents, permeationenhancers, pH-adjusting agents, preservatives, protectants, skinpenetration enhancers, softeners, solubilizers, sunscreens, sun blockingagents, sunless tanning agents, viscosity modifiers and vitamins. As isknown to one skilled in the art, in some instances a specific additionalcomponent may have more than one activity, function or effect.

In an embodiment of the present invention, the additional component is apH adjusting agent or a buffering agent. Suitable buffering agentsinclude but are not limited to acetic acid, adipic acid, calciumhydroxide, citric acid, glycine, hydrochloric acid, lactic acid,magnesium aluminometasilicates, phosphoric acid, sodium carbonate,sodium citrate, sodium hydroxide, sorbic acid, succinic acid, tartaricacid, and derivatives, salts and mixtures thereof.

In an embodiment of the present invention, the additional component isan emollient. Suitable emollients include but are not limited to mineraloil, lanolin oil, coconut oil, cocoa butter, olive oil, aloe veraextract, jojoba oil, castor oil, fatty acids, fatty alcohols,diisopropyl adipate, hydroxybenzoate esters, benzoic acid esters of C9to C15 alcohols, isononyl iso-nonanoate, silicone oils, polyethers, C12to C15 alkyl benzoates, oleic acid, stearic fatty acid, cetyl alcohols,hexadecyl alcohol, dimethyl polysiloxane, polyoxypropylene cetyl ether,polyoxypropylene butyl ether, and derivatives, esters, salts andmixtures thereof.

In an embodiment of the present invention, the additional component is ahumectant. Suitable humectants include but are not limited to guanidine,urea, glycolic acid, glycolate salts, ammonium glycolate, quaternaryalkyl ammonium glycolate, lactic acid, lactate salts, ammonium lactate,quaternary alkyl ammonium lactate, aloe vera, aloe vera gel, allantoin,urazole, polyhydroxy alcohol, sorbitol, glycerol, hexanetriol, propyleneglycol, butylene glycol, hexylene glycol, a hexylene glycol derivative,polyethylene glycol, a sugar, a starch, a sugar derivative, a starchderivative, alkoxylated glucose, hyaluronic acid, lactamidemonoethanolamine, acetamide monoethanolamine and derivatives, esters,salts and mixtures thereof.

In an embodiment of the present invention, the additional component is apreservative. Suitable preservatives include but are not limited to C12to C15 alkyl benzoates, alkyl p-hydroxybenzoates, aloe vera extract,ascorbic acid, benzalkonium chloride, benzoic acid, benzoic acid estersof C9 to C15 alcohols, butylated hydroxytoluene, castor oil, cetylalcohols, chlorocresol, citric acid, cocoa butter, coconut oil,diazolidinyl urea, diisopropyl adipate, dimethyl polysiloxane, DMDMhydantoin, ethanol, fatty acids, fatty alcohols, hexadecyl alcohol,hydroxybenzoate esters, iodopropynyl butylcarbamate, isononyliso-nonanoate, jojoba oil, lanolin oil, methylparaben, mineral oil,oleic acid, olive oil, polyethers, polyoxypropylene butyl ether,polyoxypropylene cetyl ether, potassium sorbate, silicone oils, sodiumpropionate, sodium benzoate, sodium bisulfite, sorbic acid, stearicfatty acid, vitamin E, vitamin E acetate and derivatives, esters, saltsand mixtures thereof.

In an embodiment of the present invention, the additional component is askin penetration enhancer. Suitable skin penetration enhancers includebut are not limited to acetone, acyl lactylates, acyl peptides,acylsarcosinates, alkanolamine salts of fatty acids, alkyl benzenesulphonates, alkyl ether sulphates, alkyl sulphates, anionicsurface-active agents, benzyl benzoate, benzyl salicylate,butan-1,4-diol, butyl benzoate, butyl laurate, butyl myristate, butylstearate, cationic surface-active agents, citric acid,cocoamidopropylbetaine, decyl methyl sulfoxide, decyl oleate, dibutylazelate, dibutyl phthalate, dibenzyl sebacate, dibutyl sebacate, dibutylsuberate, dibutyl succinate, dicapryl adipate, didecyl phthalate,diethylene glycol, diethyl sebacate, diethyl-m-toluamide,di(2-hydroxypropyl) ether, diisopropyl adipate, diisopropyl sebacate,N,N-dimethyl acetamide, dimethyl azelate, N,N-dimethyl formamide,1,5-dimethyl-2-pyrrolidone, dimethyl sebacate, dimethyl sulphoxide,dioctyl adipate, dioctyl azelate, dioctyl sebacate, 1,4 dioxane,1-dodecylazacyloheptan-2-one, dodecyl dimethyl amine oxides, ethylcaprate, ethyl caproate, ethyl caprylate, 2-ethyl-hexyl pelargonate,ethyl-2-hydroxypropanoate, ethyl laurate, ethyl myristate,1-ethyl-2-pyrrolidone, ethyl salicylate, hexyl laurate,2-hydroxyoctanoic acid, 2-hydroxypropanoic acid, 2-hydroxypropionicacid, isethionates, isopropyl isostearate, isopropyl palmitate, guarhydroxypropyltrimonium chloride, hexan-2,5-diol, khellin, lamepons,lauryl alcohol, maypons, metal salts of fatty acids, methyl nicotinate,2-methyl propan-2-ol, 1-methyl-2-pyrrolidone, 5-methyl-2-pyrrolidone,methyl taurides, miranol, nonionic surface-active agents, octyl alcohol,octylphenoxy polyethoxyethanol, oleic ethanolamide, pleyl alcohol,pentan-2,4-diol, phenoxyethanol, phosphatidyl choline, phosphine oxides,polyalkoxylated ether glycollates, poly(diallylpiperidinium chloride),poly(dipropyldiallylammonium chloride), polyglycerol esters,polyoxyethylene lauryl ether, polyoxy:polyoxyethylene stearate,polyoxypropylene 15 stearyl ether, poly(vinyl pyridinium chloride),propan-1-ol, propan-2-ol, propylene glycol dipelargonate, pyroglutamicacids, 2-pyrrolidone, pyruvic acids, Quaternium 5, Quaternium 18,Quaternium 19, Quaternium 23, Quaternium 31, Quaternium 40, Quaternium57, quartenary amine salts, quaternised poly(dimethylaminoethylmethacryl- ate), quaternised poly (vinyl alcohol),sapamin hydrochloride, sodium cocaminopropionate, sodium dioctylsulphonsuccinate, sodium laurate, sodium lauryl ether sulphate, sodiumlauryl sulphate, sugar esters, sulphosuccinate, tetrahydrofuran,tetrahydrofurfural alcohol, transcutol, triethanolamine dodecyl benzenesulphonate, triethanolamine oleate, urea, water and derivatives, esters,salts and mixtures thereof.

Propellants

Examples of suitable propellants include volatile hydrocarbons such asbutane, propane, isobutane and fluorocarbon gases, or mixtures thereof.

In certain embodiments, fluorohydrocarbon propellants, other thanchloro-fluoro carbons (CMOs) which are non-ozone-depleting propellants,are particularly useful in the production of a non-flammable foamablecomposition.

Such propellants include, but are not limited to hydrofluorocarbon (HFC)propellants, that contain no chlorine atoms, and as such, fallscompletely outside concerns about stratospheric ozone destruction bychlorofluorocarbons or other chlorinated hydrocarbons. Exemplarynon-flammable propellants according to this aspect of the inventioninclude propellants made by DuPont under the registered trademark Dymel,such as 1,1,1,2 tetrafluorethane (Dymel 134), and 1,1,1,2,3,3,3heptafluoropropane (Dymel 227), 1,1, difluoro ethane (Dymel 152) and1,1,1,3,3,3 hexafluoropropane. HFCs possess Ozone Depletion Potential of0.00 and thus, they are allowed for use as propellant in aerosolproducts.

The propellant makes up about 5-25 wt% of the foamable composition.Aerosol propellants are used to generate and administer the foamablecomposition as a foam. The total composition including propellant,foamable compositions and optional ingredients is referred to as thefoamable composition.

Composition and Foam Physical Characteristics and Advantages

A pharmaceutical or cosmetic composition manufactured using the foamablecarrier of the present invention is very easy to use. When applied ontothe afflicted body surface of mammals, i.e., humans or animals, it is ina foam state, allowing free application without spillage. Upon furtherapplication of a mechanical force, e.g., by rubbing the composition ontothe body surface, it freely spreads on the surface and is rapidlyabsorbed.

The foamable composition of the present invention is stable, having anacceptable shelf-life of at least one year, or preferably, at least twoyears at ambient temperature, as revealed in accelerated stabilitytests. Organic carriers and propellants tend to impair the stability ofemulsions and to interfere with the formation of a stable foam uponrelease from a pressurized container. It has been observed, however,that the foamable compositions according to the present invention aresurprisingly stable. Following accelerated stability studies, theydemonstrate desirable texture; they form fine bubble structures that donot break immediately upon contact with a surface, spread easily on thetreated area and absorb quickly.

The composition should also be free flowing, to allow it to flow throughthe aperture of the container, e.g., and aerosol container, and createan acceptable foam.

Foam quality can be graded as follows:

Grade E (excellent): very rich and creamy in appearance, does not showany bubble structure or shows a very fine (small) bubble structure; doesnot rapidly become dull; upon spreading on the skin, the foam retainsthe creaminess property and does not appear watery.

Grade G (good): rich and creamy in appearance, very small bubble size,“dulls” more rapidly than an excellent foam, retains creaminess uponspreading on the skin, and does not become watery.

Grade FG (fairly good): a moderate amount of creaminess noticeable,bubble structure is noticeable; upon spreading on the skin the productdulls rapidly and becomes somewhat lower in apparent viscosity.

Grade F (fair): very little creaminess noticeable, larger bubblestructure than a “fairly good” foam, upon spreading on the skin itbecomes thin in appearance and watery.

Grade P (poor): no creaminess noticeable, large bubble structure, andwhen spread on the skin it becomes very thin and watery in appearance.

Grade VP (very poor): dry foam, large very dull bubbles, difficult tospread on the skin.

Topically administrable foams are typically of quality grade E or G,when released from the aerosol container. Smaller bubbles are indicativeof more stable foam, which does not collapse spontaneously immediatelyupon discharge from the container. The finer foam structure looks andfeels smoother, thus increasing its usability and appeal.

As further aspect of the foam is breakability. The breakable foam isthermally stable, yet breaks under sheer force. Sheer-force breakabilityof the foam is clearly advantageous over thermally induced breakability.Thermally sensitive foams immediately collapse upon exposure to skintemperature and, therefore, cannot be applied on the hand and afterwardsdelivered to the afflicted area.

The foam of the present invention has several advantages, when comparedwith hydroalcoholic foam compositions, such as described in WO2004/071479:

(1) Breakability. The foam of the present invention is thermally stable.Unlike hydroalcoholic foam compositions of the prior art, the foam ofthe present invention is not “quick breaking”, i.e., it does not readilycollapse upon exposure to body temperature environment. Sheer-forcebreakability of the foam is clearly advantageous over thermally inducedbreakability, since it allows comfortable application and well directedadministration to the target area.

(2) Skin drying and skin barrier function. short chain alcohols areknown to dry the skin and impair the integrity of the skin barrier. Bycontrast, including a film forming agent in the composition of thepresent invention foes not cause unwanted skin barrier damage.

(3) Irritability. Due to the lack of alcohol and improvement in skinbarrier function, skin irritability is eliminated.

Another property of the foam is specific gravity, as measured uponrelease from the aerosol can. Typically, foams have specific gravity ofless than 0.12 g/mL; or less than 0.10 g/mL; or less than 0.08 g/mL,depending on their composition and on the propellant concentration.

Active Agents

In an embodiment of the present invention, an active agent inincorporated in the foamable saccharide composition.

Suitable active agents include but are not limited to active herbalextracts, acaricides, age spot and keratose removing agents, allergen,analgesics, local anesthetics, antiacne agents, antiallergic agents,antiaging agents, antibacterials, antibiotics, antiburn agents,anticancer agents, antidandruff agents, antidepressants, antidermatitisagents, antiedemics, antihistamines, antihelminths, antihyperkeratolyteagents, antiinflammatory agents, antiirritants, antilipemics,antimicrobials, antimycotics, antiproliferative agents, antioxidants,anti-wrinkle agents, antipruritics, antipsoriatic agents, antirosaceaagents antiseborrheic agents, antiseptic, antiswelling agents, antiviralagents, antiyeast agents, astringents, topical cardiovascular agents,chemotherapeutic agents, corticosteroids, dicarboxylic acids,disinfectants, fungicides, hair growth regulators, hormones, hydroxyacids, immunosuppressants, immunoregulating agents, insecticides, insectrepellents, keratolytic agents, lactams, metals, metal oxides,mitocides, neuropeptides, non-steroidal anti-inflammatory agents,oxidizing agents, pediculicides, photodynamic therapy agents, retinoids,sanatives, scabicides, self tanning agents, skin whitening agents,asoconstrictors, vasodilators, vitamins, vitamin D derivatives, woundhealing agents and wart removers. As is known to one skilled in the art,in some instances a specific active agent may have more than oneactivity, function or effect.

Hygroscopic Property of the Composition

A hydroscopic substance is a substance that absorbs water readily fromits surroundings. Microorganisms require water to grow and reproduce,and such water requirements are best defined in terms of water activityof the substrate. The water activity of a solution is expressed asAw=P/Po, where P is the water vapor pressure of the solution and Po isthe vapor pressure of pure water at the same temperature. Addition of ahygroscopic substance to an aqueous solution in which a microorganism isgrowing will have the effect of lowering the Aw, with a consequenteffect upon cell growth. Every microorganism has a limiting Aw, belowwhich it will not grow, e.g., for streptococci, klebsiella spp.,escherichia coli, clostridium perfringens, and pseudomonas spp. the Awvalue is 0.95. Staphylococcus aureus is most resistant and canproliferate with an Aw as low as 0.86.

The water activity of a product can be determined from the relativehumidity of the air surrounding the sample when the air and the sampleare at equilibrium. Measurement is performed by placing a sample in anenclosed space where this equilibrium can take place. Once this occurs,the water activity of the sample and the relative humidity of the airare equal. The measurement taken at equilibrium is called an equilibriumrelative humidity or ERH. The relationship between the water activityand ERH is in accordance with the following formula:

Aw=ERH/100

Various types of water activity instruments are commercially available.One exemplary instrument uses chilled-mirror dewpoint technology whileother instruments measure relative humidity with sensors that changeelectrical resistance or capacitance.

Saccharides have a great affinity for water, and as such, they exhibithygroscopic properties; and the concentration of the saccharidedetermines the Aw of the carrier. As such, additions of saccharides tothe composition can have a dramatic affect on Aw. In one or moreembodiments, the saccharide is contained in the composition of thepresent invention at a sufficient concentration to provide an Aw valueof the foamable composition of less than 0.9. In other embodiments, theconcentration of the hygroscopic substance in the composition isselected to provide a Aw value selected from the ranges of (1) about 0.8and about 0.9; (2) about 0.7 and about 0.8; and (3) less than about 0.7.

A saccharide composition having a water activity that is less than thatwhich can support microbial growth can be used as topical treatment ofsuperficial infectious conditions.

By providing a saccharide composition in a pressurized packaging this isisolated from the environment until immediately before use, the Aw ofthe composition is maintained. In comparison, other dosage forms such assolutions, creams, lotions, ointments and the like, involve repeatedopening of the package closure, resulting in absorption of water fromthe surrounding environment and a subsequent elevation of the Aw (thuslowering the hygroscopicity of the product, and therefore decreasing itsanti-infective potential). By contrast, a pressurized packaging does notallow for any humidity to be absorbed by the preparation, and therefore,the hygroscopic character of the composition cannot be damaged.

The Saccharide Composition As Carrier of an Anti-infective Agent

In one or more embodiments, the saccharide composition of the presentinvention further contains an anti-infective agent, selected from thegroup of an antibiotic agent, an antibacterial agent, an antifungalagent, an agent that controls yeast, an antiviral agent and anantiparasitic agent. Combining the anti-infective effect of a saccharidecomposition, which acts through a dehydration mechanism, with anadditional anti-infective agent that acts through alternate mechanismsresults in a synergistic effect and consequently higher success rate ofthe treatment.

The terms “antibacterial” and “antibiotic” as used herein shall include,but are not limited to, any substance being destructive to or inhibitingthe growth of bacteria or any substance having the capacity to inhibitthe growth of or to destroy bacteria, and are used in the treatment ofinfectious diseases. In one or more embodiments, the antibiotic agent isselected from the group consisting of a beta-lactam antibiotic, anaminoglycoside, an ansa-type antibiotic, an anthraquinone, an azole,metronidazole, an antibiotic glycopeptide, a macrolide, erythromycin,clindamycin, an antibiotic nucleoside, an antibiotic peptide, polymyxinB, an antibiotic polyene, an antibiotic polyether, an antibioticquinolone, an antibiotic steroid, fucidic acid, mupirocin,chloramphenicol, a sulfonamide, tetracycline, an antibiotic metal,silver, copper, zinc, mercury, tin, lead, bismuth, cadmium, chromium, anoxidizing agent, iodine, iodate, a periodate, a hypochlorite, apermanganate, a substance that release free radicals and/or activeoxygen, a cationic antimicrobial agent, a quaternary ammonium compound,a biguanide, chlorohexidine, a triguanide, a bisbiguanide, a polymericbiguanide, a naturally occurring antibiotic compound and analogs,derivatives, salts, ions and complexes thereof.

The terms “antifungal” as used herein shall include, but is not limitedto, any substance being destructive to or inhibiting the growth of fungiand yeast or any substance having the capacity to inhibit the growth ofor to destroy fungi and/or yeast.

In one or more embodiments, the antifungal agent is an agent that isuseful in the treatment of a superficial fungal infection of the skin,dermatophytosis, microsporum, trichophyton and epidermophytoninfections, candidiasis, oral candidiasis (thrush), candidiasis of theskin and genital mucous membrane, candida paronychia, which inflicts thenail and nail bed and genital and vaginal candida, which inflictgenitalia and the vagina. We have unexpectedly discovered that asaccharide composition containing an antifungal drug is more effectivethat other compositions, comprising the same concentration of theantifungal agent, which is not hygroscopic. Furthermore, we havediscovered that an antifungal agent, which is known to be effectiveagainst dermatophites but not against candida, becomes effective againstcandida, when it is included in a saccharide composition, as describedherein.

There is no particular limitation on the antifungal agents used in thecompositions of this invention. By way of example, preferred suitableantifungal agents be made of polyenes, e.g., natamycin, nystatin;allylamines, e.g., naftifine, terbinafine; imidazoles, e.g., bifonazole,clotrimazole, econazole, fenticonazole, ketocanazole, miconazole,oxiconazole; diazole, triazoles, e.g., fluconazole, itraconazole,terconazole, tolnaftate, ciclopirox, undecylenic acid, sulbentine,griseofulvin, Amphotericin B, flucytosine (5FC), and morpholines, e.g.,amorolfine, and the related morpholines and analogs, derivatives andsalts thereof, and any combination thereof at a therapeuticallyeffective concentration.

Any known antiviral agent, in a therapeutically effective concentration,can be incorporated in the foam composition according to one or moreembodiments of the present invention.

Thus, in preferred embodiments of the present invention a pharmaceuticalcomposition is provided, including:

(i) a saccharide aqueous solution;

(ii) about 0.2% to about 5% by weight of a surface-active agent;

(iii) about 0.01% to about 5% by weight of at least one polymeric agentselected from a bioadhesive agent, a gelling agent, a film forming agentand a phase change agent;

(iv) a therapeutically effective concentration of an anti-infectiveagent; and

(v) a liquefied or compressed gas propellant at a concentration of about3% to about 25% by weight of the total composition.

In one or more embodiments, the pharmaceutical composition furthercontains a penetration enhancer.

FIELDS OF APPLICATIONS

The foamable carrier of the present invention is suitable for treatingany infected surface. In one or more embodiments, foamable carrier issuitable for administration to the skin, a body surface, a body cavityor mucosal surface, e.g., the mucosa of the nasal cavity, the mouth, theeye, the ear canal, the vagina and the rectum (severally andinterchangeably termed herein “target site”).

By selecting a suitable active agent, or a combination of at least twoactive agents, the foamable composition of the present invention isuseful in treating an animal or a human patient having any one of avariety of dermatological disorders, including dermatological pain,dermatological inflammation, acne, acne vulgaris, inflammatory acne,non-inflammatory acne, acne fulminans, nodular papulopustular acne, acneconglobata, dermatitis, bacterial skin infections, fungal skininfections, viral skin infections, parasitic skin infections, skinneoplasia, skin neoplasms, pruritis, cellulitis, acute lymphangitis,lymphadenitis, erysipelas, cutaneous abscesses, necrotizing subcutaneousinfections, scalded skin syndrome, folliculitis, furuncles, hidradenitissuppurativa, carbuncles, paronychial infections, rashes, erythrasma,impetigo, ecthyma, yeast skin infections, warts, molluscum contagiosum,trauma or injury to the skin, post-operative or post-surgical skinconditions, scabies, pediculosis, creeping eruption, eczemas, psoriasis,pityriasis rosea, lichen planus, pityriasis rubra pilaris, edematous,erythema multiforme, erythema nodosum, granuloma annulare, epidermalnecrolysis, sunburn, photosensitivity, pemphigus, bullous pemphigoid,dermatitis herpetiformis, keratosis pilaris, callouses, corns,ichthyosis, skin ulcers, ischemic necrosis, miliaria, hyperhidrosis,moles, Kaposi's sarcoma, melanoma, malignant melanoma, basal cellcarcinoma, squamous cell carcinoma, poison ivy, poison oak, contactdermatitis, atopic dermatitis, rosacea, purpura, moniliasis,candidiasis, baldness, alopecia, Behcet's syndrome, cholesteatoma,Dercum disease, ectodermal dysplasia, gustatory sweating, nail patellasyndrome, lupus, hives, hair loss, Hailey-Hailey disease, chemical orthermal skin burns, scleroderma, aging skin, wrinkles, sun spots,necrotizing fasciitis, necrotizing myositis, gangrene, scarring, andvitiligo.

Likewise, the foamable composition of the present invention is suitablefor treating a disorder of a body cavity or mucosal surface, e.g., themucosa of the nose, mouth, eye, ear, respiratory system, vagina orrectum. Non limiting examples of such conditions include chlamydiainfection, gonorrhea infection, hepatitis B, herpes, HIV/AIDS, humanpapillomavirus (HPV), genital warts, bacterial vaginosis, candidiasis,chancroid, granuloma Inguinale, lymphogranuloma venereum, mucopurulentcervicitis (MPC), molluscum contagiosum, nongonococcal urethritis (NGU),trichomoniasis, vulvar disorders, vulvodynia, vulvar pain, yeastinfection, vulvar dystrophy, vulvar intraepithelial neoplasia (VIN),contact dermatitis, pelvic inflammation, endometritis, salpingitis,oophoritis, genital cancer, cancer of the cervix, cancer of the vulva,cancer of the vagina, vaginal dryness, dyspareunia, anal and rectaldisease, anal abscess/fistula, anal cancer, anal fissure, anal warts,Crohn's disease, hemorrhoids, anal itch, pruritus ani, fecalincontinence, constipation, polyps of the colon and rectum.

In an embodiment of the present invention, the composition is useful forthe treatment of an infection. In one or more embodiments, thecomposition is suitable for the treatment of an infection, selected fromthe group of a bacterial infection, a fungal infection, a yeastinfection, a viral infection and a parasitic infection.

In an embodiment of the present invention, the composition is useful forthe treatment of wound, ulcer and burn. This use is particularlyimportant since the composition of the present invention creates a thin,semi-occlusive layer, which coats the damaged tissue, while allowingexudates to be released from the tissue.

The composition of the present invention is also suitable foradministering a hormone to the skin or to a mucosal membrane or to abody cavity, in order to deliver the hormone into the tissue of thetarget organ, in any disorder that responds to treatment with a hormone.

The invention is described with reference to the following examples.This invention is not limited to these examples and experiments. Manyvariations will suggest themselves and are within the full intendedscope of the appended claims.

Example 1 Foamable Saccharide Composition Containing Sorbitol and Honey

SOR1 SOR2 HON1 % w/w % w/w % w/w Sorbitol 70% 89.50 89.50 — Honey — —89.50 Steareth 2 2.00 — — Ceteth 2 — 2.00 2.00 Hydroxyethylcellulose0.50 0.50 0.50 Propellant 8.00 8.00 8.00 Foam quality G G G

Upon release from the aerosol can a foam of Excellent quality (verysmall bubble size) is formed. The foam is stable when placed on theskin. Upon easy rubbing, the foam readily spreads on the skin and israpidly absorbed.

Example 2 Foamable Saccharide Comparison Containing Active Agents

The following active agents have been incorporated into FormulationsSOR1, SOR2 and HON1:

Terbinafine 2%;

Miconazole 1%;

Iodine-povidone 5%;

Hydrocortisone acetate 0.1%;

Clobetasol dipropionate 0.05%; and

Clindamycin 1%

Example 3 Usability Study: comparison between a foam according to thepresent invention and an ointment product.

The objective of this study was to assess the usability properties offoam product “SOR1”, in comparison with a comparator ointment. The studypanelists (n=12) were asked to test the usability of two foam products,in comparison with a comparator ointment, with regard to the followingparameters:

Ease of application

Uniform spreading

Accurate location

Skin absorption

Oily residue

Shiny residual look

Stickiness

The panelists were instructed to rate a series of usability parametersand to grade each of the foam products according to the following scale:

Score −3: Ointment is much better than the foam (Ointment>>>Foam)

Score −2: Ointment is better than the foam (Ointment>>Foam).

Score −1: Ointment is slightly better than the foam (Ointment>Foam).

Score 0: Foam as good as Ointment (Foam=Ointment)

Score +1: Foam is slightly better than the Ointment (Foam>Ointment).

Score +2: Foam is better than the Ointment (Foam>>Ointment)

Score +3: Foam is much better than the Ointment (Foam>>>Ointment).

The mean result of the comparison indicated high preference to the foamin all usability parameters, as shown in the following table:

Mean score Ease of application 1.4 Uniform spreading 0.8 Accuratelocation 0.3 Skin absorption 2.4 Oily residue 1.2 Shiny residual look1.2 Stickiness 1.1

1. A foamable composition including: (i) water; (ii) about 20% to about80% by weight of a saccharide selected from the group consisting of amonosaccharide, a disaccharide, an oligosaccharide, a sugar alcohol andmixtures thereof; or honey, in an amount that provides about 20% toabout 80% by weight of a mixture of saccharides in the composition;(iii) about 0.2% to about 5% by weight of a non-ionic surface-activeagent; and (iv) a liquefied hydrocarbon propellant or compressed gaspropellant at a concentration of about 3% to about 25% of the totalcomposition; and wherein the composition forms a breakable foam upondispensing.
 2. The composition of claim 1, further comprising a polarsolvent.
 3. The composition of claim 2, wherein the composition ishygroscopic.
 4. The composition of claim 3, wherein the composition hasan Aw value of less than 0.9 or about 0.9.
 5. The composition of claim2, wherein the polar solvent is selected from the group consisting ofpropylene glycol, butanediol, butanediol, butynediol, pentanediol,hexanediol, octanediol, neopentyl glycol, 2-methyl-1,3-propanediol,diethylene glycol, triethylene glycol, tetraethylene glycol, dipropyleneglycol, dibutylene glycol, glycerin, butane-1,2,3-triol,butane-1,2,4-triol and hexane-1,2,6-triol, dimethyl isosorbide,tetrahydrofurfuryl alcohol polyethyleneglycol ether, DMSO, apyrrolidone, N-Methyl-2-pyrrolidone, 1-Methyl-2-pyrrolidinone, ethylproxitol, dimethylacetamide, an alpha hydroxy acids, lactic acid,glycolic acid and polyethylene glycol.
 6. The composition of claim 5,wherein the polar solvent possesses skin penetration properties.
 7. Thecomposition of claim 2 further comprising a penetration enhancer.
 8. Thecomposition of claim 2, further comprising: about 0.01% to about 5% byweight of at least one polymeric agent selected from a bioadhesiveagent, a gelling agent, a film forming agent and phase change agent; ora foam adjuvant comprising a fatty alcohol or a fatty acid, or a mixturethereof.
 9. The composition of claim 2, further containing a hydrophobicsolvent.
 10. The composition of claim 9, wherein the composition is inthe form of an oil in water emulsion.
 11. The composition of claim 9,wherein the composition is in the form of a water in oil emulsion. 12.The composition of claim 1, further comprising an ionic surface-activeagent.
 13. The composition of claim 12, wherein the ratio of non-ionicto ionic surfactant is between 100:1 to 20:1.
 14. The composition ofclaim 12, wherein the ratio between the non-ionic surfactant and theionic surfactant is in a in a range selected from (i) 1:1 to 20:1; and(ii) greater than 20:1.
 15. The composition of claim 1, furthercontaining at least one active agent selected from the group of anactive herbal extract, an acaricide, an age spot and keratose removingagent, an allergen, an analgesic agent, a local anesthetic, an antiacneagent, an antiallergic agent, an antiaging agent, an anti-infectiveagent, an antifungal agent, an agent that controls yeast, anantiparasitic agent, an antibacterial agent, an antibiotic agent, anantiburn agent, an anticancer agent, an antidandruff agent, anantidepressant, an antidermatitis agent, an antiedemic agent, anantihistamine, an antihyperkeratolyte agent, an antiinflammatory agent,an antiirritant, an antilipemic agent, an antimicrobial agent, anantimycotic agent, an antiproliferative agent, an antioxidant, ananti-wrinkle agent, an antipruritic agent, an antipsoriatic agent, anantirosacea agent, an antiseborrheic agent, an antiseptic agent, anantiswelling agent, an antiviral agent, an antiyeast agent, anastringent, a topical cardiovascular agent, a chemotherapeutic agent, acorticosteroid, a dicarboxylic acid, a disinfectant, a fungicide, a hairgrowth regulator, a hormone, a hydroxy acid, an immunosuppressant, animmunoregulating agent, an insecticide, an insect repellent, akeratolytic agent, a lactam, a metal, a metal oxide, a mitocide, aneuropeptide, a non-steroidal anti-inflammatory agent, an oxidizingagent, a pediculicide, a photodynamic therapy agent, a retinoid, ascabicide, a self tanning agent, a skin whitening agent, avasoconstrictor, a vasodilator, a vitamin, a vitamin D derivative, awound healing agent and a wart remover.
 16. The composition of claim 15,wherein the antibiotic agent is selected from the group consisting of abeta-lactam antibiotic, an aminoglycoside, an ansa-type antibiotic, ananthraquinone, an azole, metronidazole, an antibiotic glycopeptide, amacrolide, erythromycin, clindamycin, an antibiotic nucleoside, anantibiotic peptide, polymyxin B, an antibiotic polyene, an antibioticpolyether, an antibiotic quinolone, an antibiotic steroid, fucidic acid,mupirocin, chloramphenicol, a sulfonamide, tetracycline, an antibioticmetal, silver, copper, zinc, mercury, tin, lead, bismuth, cadmium,chromium, an oxidizing agent, iodine, iodate, a periodate, ahypochlorite, a permanganate, a cationic antimicrobial agent, aquaternary ammonium compound, a biguanide, chlorohexidine, a triguanide,a bisbiguanide, a polymeric biguanide, a naturally occurring antibioticcompound and salts, ions and complexes thereof; or wherein theantifungal agent is useful in the treatment of an infection ofdermatophytosis, microsporum, trichophyton and epidermophytoninfections, candidiasis, oral candidiasis (thrush), yeast and candida;or wherein the antifungal agent is selected from the group consisting ofa polyene, natamycin, nystatin; an allylamine, naftifine, terbinafine;an imidazole, bifonazole, clotrimazole, econazole, fenticonazole,ketocanazole, miconazole, oxiconazole; a diazole, a triazoles,fluconazole, itraconazole, terconazole, tolnaftate, ciclopirox,undecylenic acid, sulbentine, griseofulvin, Amphotericin B, flucytosine(5FC), a morpholine compound, amorolfine, and the related morpholinesand salts thereof, and any combination thereof at a therapeuticallyeffective concentration; or wherein the keratolytic agent is selectedfrom the group consisting of urea, an alpha-hydroxy acid, lactic acid,phenol, resorcinol, salicylic acid, a keratolytic enzyme, a proteolyticenzyme and papain.
 17. A foamable composition including: (i) water; (ii)about 20% to about 80% by weight of a saccharide selected from the groupconsisting of a monosaccharide, a disaccharide, an oligosaccharide, asugar alcohol and mixtures thereof; or honey, in an amount that providesabout 20% to about 80% by weight of a mixture of saccharides in thecomposition; (iii) a polyol; (iv) about 0.2% to about 5% by weight of anon ionic surface-active agent; and (v) a liquefied hydrocarbonpropellant or compressed gas propellant at a concentration of about 3%to about 25% of the total composition; wherein the composition ishygroscopic; wherein the concentration of the saccharide and polyol issufficient to provide an Aw value less than 0.9 or about 0.9; andwherein the composition forms a breakable foam upon dispensing.
 18. Thecomposition of claim 17, further containing at least one active agentselected from the group of an active herbal extract, an acaricide, anage spot and keratose removing agent, an allergen, an analgesic agent, alocal anesthetic, an antiacne agent, an antiallergic agent, an antiagingagent, an anti-infective agent, an antifungal agent, an agent thatcontrols yeast, an antiparasitic agent, an antibacterial agent, anantibiotic agent, an antiburn agent, an anticancer agent, anantidandruff agent, an antidepressant, an antidermatitis agent, anantiedemic agent, an antihistamine, an antihyperkeratolyte agent, anantiinflammatory agent, an antiirritant, an antilipemic agent, anantimicrobial agent, an antimycotic agent, an antiproliferative agent,an antioxidant, an anti-wrinkle agent, an antipruritic agent, anantipsoriatic agent, an antirosacea agent, an antiseborrheic agent, anantiseptic agent, an antiswelling agent, an antiviral agent, anantiyeast agent, an astringent, a topical cardiovascular agent, achemotherapeutic agent, a corticosteroid, a dicarboxylic acid, adisinfectant, a fungicide, a hair growth regulator, a hormone, a hydroxyacid, an immunosuppressant, an immunoregulating agent, an insecticide,an insect repellent, a keratolytic agent, a lactam, a metal, a metaloxide, a mitocide, a neuropeptide, a non-steroidal anti-inflammatoryagent, an oxidizing agent, a pediculicide, a photodynamic therapy agent,a retinoid, a scabicide, a self tanning agent, a skin whitening agent, avasoconstrictor, a vasodilator, a vitamin, a vitamin D derivative, awound healing agent and a wart remover.
 19. A method of treatment of adisorder of a target site comprising: administering to a target site inneed of treatment, said target site selected from the group consistingof the skin, a body surface, a body cavity or mucosal surface, the nasalcavity, the mouth, the eye, the ear canal, the vagina and the rectum; acomposition comprising: (i) water; (ii) about 20% to about 80% by weightof a selected from the group consisting of a monosaccharide, adisaccharide, an oligosaccharide, a sugar alcohol and mixtures thereof;or honey, in an amount that provides about 20% to about 80% by weight ofa mixture of saccharides in the composition; (iii) optionally a polarsolvent. (iv) about 0.2% to about 5% by weight of a non ionicsurface-active agent; and a liquefied hydrocarbon propellant orcompressed gas propellant at a concentration of about 3% to about 25% ofthe total composition; wherein the composition is hygroscopic; whereinthe concentration of the saccharide and any polar solvent is sufficientto provide an Aw value less than 0.9 or about 0.9; and wherein thecomposition forms a breakable foam upon administration.
 20. The methodof claim 19, wherein the composition further comprises: about 0.01% toabout 5% by weight of at least one polymeric agent selected from abioadhesive agent, a gelling agent, a film forming agent and phasechange agent; or a foam adjuvant comprising a fatty alcohol or a fattyacid, or a mixture thereof.
 21. The method of claim 19, wherein thedisorder comprises an infection, wherein the infection is selected fromthe group consisting of a bacterial infection, a fungal infection, ayeast infection, a viral infection and a parasitic infection; and orwherein the disorder is selected from the group consisting of wound,ulcer, burn, dermatological pain, dermatological inflammation, acne,acne vulgaris, inflammatory acne, non-inflammatory acne, acne fulminans,nodular papulopustular acne, acne conglobata, dermatitis, bacterial skininfections, fungal skin infections, viral skin infections, parasiticskin infections, skin neoplasia, skin neoplasms, pruritis, cellulitis,acute lymphangitis, lymphadenitis, erysipelas, cutaneous abscesses,necrotizing subcutaneous infections, scalded skin syndrome,folliculitis, furuncles, hidradenitis suppurativa, carbuncles,paronychial infections, rashes, erythrasma, impetigo, ecthyma, yeastskin infections, warts, molluscum contagiosum, trauma or injury to theskin, post-operative or post-surgical skin conditions, scabies,pediculosis, creeping eruption, eczemas, psoriasis, pityriasis rosea,lichen planus, pityriasis rubra pilaris, edematous, erythema multiforme,erythema nodosum, granuloma annulare, epidermal necrolysis, sunburn,photosensitivity, pemphigus, bullous pemphigoid, dermatitisherpetiformis, keratosis pilaris, callouses, corns, ichthyosis, skinulcers, ischemic necrosis, miliaria, hyperhidrosis, moles, Kaposi'ssarcoma, melanoma, malignant melanoma, basal cell carcinoma, squamouscell carcinoma, poison ivy, poison oak, contact dermatitis, atopicdermatitis, rosacea, purpura, moniliasis, candidiasis, baldness,alopecia, Behcet's syndrome, cholesteatoma, Dercum disease, ectodermaldysplasia, gustatory sweating, nail patella syndrome, lupus, hives, hairloss, Hailey-Hailey disease, chemical or thermal skin burns,scleroderma, aging skin, wrinkles, sun spots, necrotizing fasciitis,necrotizing myositis, gangrene, scarring, vitiligo, chlamydia infection,gonorrhea infection, herpes, HIV/AIDS, human papillomavirus (HPV),genital warts, bacterial vaginosis, candidiasis, chancroid, granulomaInguinale, lymphogranuloma venereum, mucopurulent cervicitis (MPC),molluscum contagiosum, nongonococcal urethritis (NGU), trichomoniasis,vulvar disorders, vulvodynia, vulvar pain, yeast infection, vulvardystrophy, vulvar intraepithelial neoplasia (VIN), contact dermatitis,pelvic inflammation, endometritis, salpingitis, oophoritis, genitalcancer, cancer of the cervix, cancer of the vulva, cancer of the vagina,vaginal dryness, dyspareunia, anal and rectal disease, analabscess/fistula, anal cancer, anal fissure, anal warts, Crohn's disease,hemorrhoids, anal itch, pruritus ani, fecal incontinence, constipation,polyps of the colon and rectum.
 22. A method for delivering acomposition, comprising (a) charging a container with a compositioncomprising a foamable carrier and a liquefied or compressed gashydrocarbon propellant, wherein the propellant is present at aconcentration of about 3% to about 25% by weight of the totalcomposition, and wherein the carrier comprises (i) water; (ii) about 20%to about 80% by weight of a saccharide selected from the groupconsisting of a monosaccharide, a disaccharide, an oligosaccharide, asugar alcohol and mixtures thereof; (iii) optionally honey, in an amountthat provides about about 20% to about 80% by weight of a mixture ofsaccharides in the composition; (iv) optionally a polar solvent; (v)about 0.2% to about 5% by weight of a non ionic surface-active agent;and (b) dispensing the composition onto a body surface or in a bodycavity, wherein the composition is hygroscopic; wherein theconcentration of the saccharide and any polar solvent is sufficient toprovide an Aw value less than 0.9 or about 0.9; and wherein thecomposition is dispensed as a breakable foam.
 23. The method of claim22, wherein the carrier further comprises: about 0.01% to about 5% byweight of at least one polymeric agent selected from a bioadhesiveagent, a gelling agent, a film forming agent and phase change agent; ora foam adjuvant comprising a fatty alcohol or a fatty acid, or a mixturethereof.
 24. The method of claim 22, wherein the breakable foam createsa semi-occlusive layer on the surface or body cavity.
 25. A foamablecomposition including: (i) water; (ii) about 20% to about 80% by weightof a sugar alcohol; (iii) optionally a polar solvent; (iv) about 0.2% toabout 5% by weight of a non ionic surface-active agent; (v) about 0.01%to about 5% by weight of at least one foam adjuvant; and (vi) aliquefied hydrocarbon propellant or compressed gas propellant at aconcentration of about 3% to about 25% of the total composition, andwherein the composition is hygroscopic; wherein the concentration of thesaccharide and any polar solvent is sufficient to provide an Aw valueless than 0.9 or about 0.9; and and wherein the composition forms abreakable foam upon dispensing.
 26. The foamable composition of claim 1,further comprising: one or more additional components selected from thegroup consisting of anti perspirants, anti-static agents, bufferingagents, bulking agents, chelating agents, cleansers, colorants,conditioners, deodorants, diluents, dyes, emollients, fragrances, hairconditioners, humectants, occlusive agents, oils, penetration enhancers,pearlescent aids, perfuming agents, permeation enhancers, pH-adjustingagents, preservatives, protectants, softeners, solubilizers, sunscreens,sun blocking agents, sunless tanning agents, viscosity modifiers andvitamins.
 27. The foamable composition of claim 17 further comprising:one or more additional components selected from the group consisting ofanti perspirants, anti-static agents, buffering agents, bulking agents,chelating agents, cleansers, colorants, conditioners, deodorants,diluents, dyes, emollients, fragrances, hair conditioners, humectants,occlusive agents, oils, penetration enhancers, pearlescent aids,perfuming agents, permeation enhancers, pH-adjusting agents,preservatives, protectants, softeners, solubilizers, sunscreens, sunblocking agents, sunless tanning agents, viscosity modifiers andvitamins.